The following description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
Breast cancer, as the name implies, refers to cancers that form in breast tissue, primarily in milk ducts and lobules. Although rare in males, it can occur in either gender. It is the most common form of cancer in women and is second only to lung cancer in terms of fatality. While breast cancer rates have been decreasing since 2000 it is estimated that approximately 1 in 8 women in the United States will develop invasive breast cancer. Approximately 5% to 10% of breast cancers are thought to be linked to inherited genetic mutations, the most well known being mutations to the BRCA1 and BRCA2 genes. The majority of breast cancers do not appear to be associated with inherited mutations, and are thought to be due to mutations that occur due to aging and environmental exposure.
Currently breast cancer is diagnosed by imaging and cytology of biopsied specimens, which usually follows from abnormal findings from self examination or from screening (for example, mammograms, breast MRI, and breast ultrasound examination). Such methods, however, may not provide complete information regarding prognosis, what treatment modalities may be more effective, and the likelihood of reoccurrence.
More recently approaches have been developed that utilize mutation analysis to more accurately identify cancerous or neoplastic cells and to provide a more complete clinical picture for the physician. Such approaches can address inherited mutations (for example, BRCA1 and BRCA2), but can also address mutations acquired through aging and environmental exposure. For example, United States Patent Application US 2010/0,255,470 (to Bankaitis-Davis et al) describes the use of expression profiling of TP53 for the characterization of suspected neoplastic cells. All publications identified herein are incorporated by reference to the same extent as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. Where a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply.
Similarly, European Patent Application 2,083,088A2 (to Lai and Fanidi) discusses expression profiling of TP53 and numerous other potential cancer markers for the diagnosis of breast and other cancers. Identification of specific mutations of TP53 have also been proposed for assessing susceptibility to breast cancer (United States Patent Application 2011/0,015,081, to Stacey et al). TP53 is mutated in approximately 50% of cancers, however, so while characterization of this gene may have utility it may lack specificity.
Specificity can potentially be improved by characterizing more than one genetic marker. For example, International Patent Application 2013/075059 A1 (to Pietenpol) discusses characterization of the expression profiles of groups of genetic markers in the characterization of breast cancer. United States Patent Application 2014/0,121,128 (to del Sal et al) discusses characterization of a specific TP53 variant in combination with expression profiling of 10 ore other genes for determining the prognosis of a person with breast cancer. Similarly, International Patent Application 2012/092,426 A1 (to Downing et al) and International Patent Application 2014/004,726 A1 (to Chen et al) discuss identifying 20 or more specific mutations, including mutations in TP53, to diagnose or otherwise characterize a variety of cancers, including breast cancer. United States Patent Application 2013/0,143,747 (to Gutin et al) discusses the use of information from the Catalogue of Somatic Mutations in Cancer to identify specific mutations of TP53 that can be used in combination with specific mutations of APC, KRAS, BRAF, and EGFR in the diagnosis of various cancers, including breast cancer.
Such approaches, however, have their shortcomings. Expression profiling, for example, requires accurate quantitation of the gene product (i.e. RNA), which in turn involves accurate reverse transcription and amplification to provide useful data. Such accurate quantitation can be difficult to achieve, particularly from clinical specimens. Accurate identification of numerous specific mutations carries similar risks, particularly where an erroneous individual result can impact the analysis.
Thus, there is still a need for a method of characterizing a sample from a breast cancer or other cancer using a limited number of genetic markers, and for a method of identifying such markers.